The central purpose of this research plan is to define further the dynamics of lead transport in children. To this end, the primary focus is to clarify factors that determine the movement of lead into and out of bone, where over 90 percent of endogenous lead is stored. This cardinal phase of the research plan will be carried out in bone organ culture, a convenient and precise way to study the effects of the ionic milieu and hormonal peptides that regulate lead's efflux from bone. Complementary in vitro experiments will examine: 1) The role of chick calcium-binding protein in the intestinal absorption of lead, and 2) The effects of ionized calcium (Ca ions) and lanthanum (La) on the mechanisms of lead movement from red cell to plasma. Integration of data obtained from in vitro studies will be applied to construct different chelation regimens, for the treatment of lead- intoxicated rats, by adding to such therapy combinations of Ca ions, calcitonin (CT), and parathyroid hormone (PTH). This comprehensive research plan, focusing on the skeletal metabolism of lead, presumably, will define more clearly the kinetics of lead transport. By so doing, the potential hazards of "subtoxic" doses of lead may be understood, and more effective therapy may evolve for the treatment of childhood lead intoxication.